GENETIC PREDISPOSITION TO PRE-ECLAMPSIA:
POLYMORPHISM OF GENES INVOLVED IN
REGULATION OF ENDOTHELIAL FUNCTIONS
Mozgovaia EV, Malysheva OV, Ivashchenko TE, Baranov VS*
*Corresponding Author: Professor Dr. Vladislav S. Baranov, Laboratory of Prenatal Diagnosis of Inherited Disorders, D.O. Ott Research Institute of Obstetrics and Gynecology, Russian Academy of Medical Sciences, Mendeleevskaya line 3, St. Petersburg 199034, Russia; Tel/Fax: +07-812-328-0487; E-mail: baranov@vb2475. spb.edu
page: 19
|
|
CONCLUSIONS
Our data substantiate existing opinions that PE represents a complex syndrome which include various pathological conditions that produce similar clinical traits, but developing in different ways. Far from being considered as a single clinical diagnosis, PE should be divided into different subgroups according to its metabolic and genetic bases.
The present data show that particular genotypes of the tested genes are associated with the development of particular clinical forms of PE, and thus contribute to the genetic background of this disease. The following genotypes: I/I (PLAT), 4G/4G (PAI-1), 4a/4a (eNOS), A/G (TNF-a, and 1c/1c (GSTP1) should be considered as markers of unfavorable prognosis at onset of PE, if they are combined with arterial hypertension, kidney disorders or with diabetes mellitus. Progression of pPE is also associated with particular polymorphisms of the same genes, although usually with some other genotypes such as D/D (ACE), 4b/4b (eNOS), G/G (TNF-a, and 1a/1a (GSTP1). Correlation of certain genotypes for PLAT, PAI and especially TNF-a, with endothelial dysfunction induced by some other diseases which existed before pregnancy, is also quite obvious. In these cases, PE comes as a primary clinical manifestation of a previous chronic endothelial dysfunction acquired before pregnancy. However, a final conclusion about the actual impact of some unfavorable combinations of the genes participating in endothelial function in the origin of PE should be considered premature and deserves further study.
Analysis of other gene groups involved in the possible pathogenesis of PE should be undertaken. These could include: 1) genes whose products are responsible for immunological and intercellular interactions during implantation and placentation, and 2) genes responsible for placental growth such as vascular endothelial growth factor (VEGF), placental growth factor (PGF), angiopoietins and angiostatins [16]. According to the present data, early testing for genetic polymorphisms relevant to endothelial dysfunction could be rather important for presymptomatic identification of women at high risk for PE.
Table 2. Polymorphisms of the ACE, eNOS and TNF-a genes in pregnant women with pre-eclampsia.
|
ACE Polymorphism |
n |
Genotype
I/I (%) |
Genotype
I/D (%) |
Genotype
D/D (%) |
c2 |
OR |
|
Control group |
73 |
10.9 |
50.6 |
38.3 |
|
|
|
Pure PE
- nephropathia I & II
- severe
|
45
34
11 |
22.2
23.5
18.1 |
31.1
20.5
63.6 |
46.6
55.8
18.1 |
5.25 (p<0.25)
9.18 (p<0.05)
1.81 |
1.4
2.04
0.35
1.7 |
|
Combined PE
- mild with mild AH
- mild with severe AH
- severe with mild AH
- severe with heavy AH
- with kidney disease
- with type 1 diabetes
- with type 2 diabetes
|
73
21
12
12
11
16
9
4 |
20
28.5
25.0
46.1
0.0
12.5
22.2
25.0 |
46.2
33.3
25.0
38.4
45.4
56.2
77.7
25.0 |
33.7
38.0
50.0
15.3
54.5
31.2
0.0
50.0 |
2.37 (p<0.5)
4.45 (p<0.25)
3.36 (p<0.5)
10.4 (p<0.05)
1.87
0.29
5.38 (p<0.25) |
0.81
0.99
1.6
0.32
1.9
3.41.6 |
|
eNOS Polymorphism |
n |
Genotype
4a/4a (%) |
Genotype
4a/4b (%) |
Genotype
4b/4b (%) |
c2 |
OR |
|
Control group |
73 |
2.7 |
33.3 |
63.8 |
|
|
|
Pure PE
- nephropathia I & II
- severe
|
42
31
11 |
0.0
0.0
0.0 |
30.9
40.0
0.0 |
69.1
60.0
100.0 |
1.35
0.19
8.2 (p<0.05) |
0.89‚
1.47‚ |
|
Combined PE
- mild with mild AH
- mild with severe AH
- severe with mild AH
- severe with severe AH
- with kidney disease
- with type 1 diabetes
- with type 2 diabetes
- with gestational diabetes
|
76
17
12
12
12
14
10
4
5 |
3.9
11.2
0.0
0.0
0.0
0.0
10.0
0.0
0.0 |
38.1
50.0
50.0
58.3
25.0
28.5
30.0
50.0
40.0 |
57.8
38.8
50.0
41.6
75.0
71.4
60.0
50.0
60.0 |
0.6
4.87 (p<0.25)
1.45
2.9 (p<0.5)
0.75
0.51
1.3 |
1.46
4.38
2.0‚
2.8‚
0.67‚
3.89
2.0‚
1.33‚ |
|
TNF-a Polymorphism |
n |
Genotype
(–238) G/G (%) |
Genotype
(–238) A/G (%) |
c2 |
OR |
|
Control group |
73 |
91.7 |
8.2 |
|
|
|
Pure PE
- nephropathia I & II
- severe
|
41
26
15 |
92.6
88.4
100.0 |
7.3
11.5
0.0 |
0.036
0.011
0.345 |
0.85
1.46 |
|
Combined PE
- nephropathia I with mild AH
- nephropathia II & III with mild AH
- real PE with mild AH
- with severe AH
- heavy with kidney disease
- with gestational diabetes
|
76
22
11
4
25
10
5 |
84.0
63.6
85.7
75.0
100.0
50.0
80.0 |
16.0
36.3
14.2
25.0
0.0
50.0
20.0 |
1.44 (p<0.5)
8.53 (p<0.05)
0.07
0.18
9.97 (p<0.05) |
1.75
6.38
1.6
3.72
11.2
2.79 |
|
GSTP1 Polymorphism |
n |
Genotype
1a/1a (%) |
Genotype
1a/1b (%) |
Genotype
1a/1c (%) |
Genotype
1b/1b (%) |
Genotype
1b/1c (%) |
Genotype
1c/1c (%) |
c2 |
OR |
|
Control group |
73 |
53.3 |
26.0 |
9.5 |
6.8 |
4.1 |
0.0 |
|
|
|
Pure PE
- nephropathia I and II
- severe
|
45
30
15 |
48.8
40.0
62.5 |
35.5
43.3
25.0 |
8.8
6.6
12.5 |
0.0
0.0
0.0 |
2.2
3.3
0.0 |
4.6
6.6
0.0 |
4.35 (p<0.5)
5.12 (p<0.5)
2.07 |
1.57
2.17
1.45‚ |
|
Combined PE
- mild with mild AH
- mild with severe AH
- severe with mild AH
- severe with severe AH
- with type 2 diabetes and gestational diabetes
|
77
19
12
12
12
16
9 |
46.7
42.1
50.0
75.0
25.0
62.6
22.2 |
24.6
26.3
25.0
0.0
25.0
12.5
33.3 |
19.4
26.3
16.6
16.6
33.3
18.7
33.3 |
5.1
5.2
8.3
0.0
8.3
0.0
0.0 |
2.5
0.0
0.0
0.0
8.3
6.2
0.0 |
1.2
0.0
0.0
8.3
0.0
0.0
11.1 |
4.24
4.45 (p<0.05)
1.04
5.78 (p<0.5)
6.6 (p<0.05)
3.42
6.4 (p<0.5) |
2.29‚
3.37‚
1.89‚
1.24ƒ
1.89‚
4.71‚
1.24ƒ
2.12„
2.18‚
1.56„
4.7‚ |
Table 3. Polymorphisms of the GSTP1 genes in pregnant women with pre-eclampsia.
|
|
|
|
 |
Number 27
VOL. 27 (2), 2024 |
Number 27
VOL. 27 (1), 2024 |
Number 26
Number 26 VOL. 26(2), 2023 All in one |
Number 26
VOL. 26(2), 2023 |
Number 26
VOL. 26, 2023 Supplement |
Number 26
VOL. 26(1), 2023 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
